Recipient hypertonic saline infusion prevents cardiac allograft dysfunction

Objective

Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.

The Importance of Venous Return in Starling‐Like Control of Rotary Ventricular Assist Devices

Rotary ventricular assist devices (VADs) are less sensitive to preload than the healthy heart, resulting in inadequate flow regulation in response to changes in patient cardiac demand. Starling‐like physiological controllers (SLCs) have been developed to automatically regulate VAD flow based on ventricular preload. An SLC consists of a cardiac response curve (CRC) which imposes a nonlinear relationship between VAD flow and ventricular preload, and a venous return line (VRL) which determines the return path of the controller. This study investigates the importance of a physiological VRL in SLC of dual rotary blood pumps for biventricular support. Two experiments were conducted on a physical mock circulation loop (MCL); the first compared an SLC with an angled physiological VRL (SLC‐P) against an SLC with a vertical VRL (SLC‐V). The second experiment quantified the benefit of a dynamic VRL, represented by a series of specific VRLs, which could adapt to different circulatory states including changes in pulmonary (PVR) and systemic (SVR) vascular resistance versus a fixed physiological VRL which was calculated at rest. In both sets of experiments, the transient controller responses were evaluated through reductions in preload caused by the removal of fluid from the MCL. The SLC‐P produced no overshoot or oscillations following step changes in preload, whereas SLC‐V produced 0.4 L/min (12.5%) overshoot for both left and right VADs. Additionally, the SLC‐V had increased settling time and reduced controller stability as evidenced by transient controller oscillations. The transient results comparing the specific and standard VRLs demonstrated that specific VRL rise times were improved by between 1.2 and 4.7 s ( = 3.05 s), while specific VRL settling times were improved by between 2.8 and 16.1 seconds ( = 8.38 s) over the standard VRL. This suggests only a minor improvement in controller response time from a dynamic VRL compared to the fixed VRL. These results indicate that the use of a fixed physiologically representative VRL is adequate over a wide variety of physiological conditions.     

UPLC-MS/MS测定73例患者血中头孢哌酮与舒巴坦的浓度

目的：建立液相色谱-串联质谱法（UPLC-MS/MS）同时测定人血浆中头孢哌酮与舒巴坦的浓度，分析头孢哌酮/舒巴坦血药浓度监测结果，为临床合理用药提供参考。方法：以氯唑沙宗为内标，采用Waters BEHC₁₈柱（2.1 mm×100 mm，1.7 μm）进行分离，通过串联质谱仪，负离子检测模式下，以多反应监测（MRM）方式进行定量测定。对某院2018年以不同给药方案进行治疗的73例住院患者测定的头孢哌酮/舒巴坦血药浓度结果进行分析。结果：头孢哌酮与舒巴坦在测定条件下1~200 mg·L^-1范围内线性关系良好，两者日内精密度RSD均<10%，基质效应分别为（72.77±0.99）%与（75.72±0.11）%，提取回收率均>90%。73例患者共监测血药浓度96次，其中不同给药方案2 g，q8 h（43例次）；2 g，q12 h（26例次）；2 g，q6 h（27例次），各组头孢哌酮血药浓度的中位数分别为34.12 mg·L^-1（4.12~177.79 mg·L^-1）、31.23 mg·L^-1（1.89~251.8 mg·L^-1）、59.96 mg·L^-1（1.77~140.58 mg·L^-1），舒巴坦血药浓度的中位数分别为6.3 mg·L^-1（0.61~136.01 mg·L^-1）、28.83 mg·L^-1（0.5~133.69 mg·L^-1）、11.17 mg·L^-1（0.73~143.53 mg·L^-1）。Mann-Whitney U检验显示，头孢哌酮血药浓度结果无统计学差异（P>0.05），舒巴坦有统计学差异（P<0.05）。结论：本检测方法操作简便、快速、重复性好，可满足临床头孢哌酮与舒巴坦浓度的检测；头孢哌酮/舒巴坦在不同给药方案下血药浓度结果与个体差异相关，有必要开展血药浓度监测并依据结果适时调整用药方案，提高治疗效果减少耐药率的发生。     

How Do Students Source and Supply Drugs? Characteristics of the University Illegal Drug Trade

Background: It is widely known that a proportion of university students use drugs. However, much less is known about how they source and supply their drugs. Objectives: In this article, we investigate student drug trading activity, including how they obtained their drugs, whether they sold drugs, and the extent to which their drug trading might be described as a form of “social supply”. Methods: A survey was conducted of all students across seven of the nine universities of Wales. In total, 7855 students submitted a questionnaire and 1877 of these reported drug use in the current academic year. All students who reported using one or more illegal drugs in the current academic year were asked how they obtained their drugs, how they funded their drug use, whether they had sold, traded or given away illegal drugs, along with their motives for drug trading. Results: The results showed that about half of users obtained drugs solely from friends and associates and one-fifth obtained them solely from external dealers. One-quarter used friends and associates as well as external markets. In many cases, supplying drugs amounted to sharing them or giving them away. However, over one-third of students said that they had sold drugs. Conclusions: Overall, the methods of sourcing and supplying drug among university students shares features of both “social supply” and “traditional” drug markets. We conclude that the student drug market investigated is best described as a “hybrid” combination of both.     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

高通量血液透析和低通量血液透析不同模式对老年维持性血液透析患者血压的影响

目的 观察高通量血液透析(HFHD)与低通量血液透析(LFHD)的不同模式运用到老年患者维持性血液透析(MHD)中对其血压的影响。方法 选择2015年2月—2017年10月本院治疗的MHD老年患者74例,先为其施LFHD 3个月,再为其辅以3个月的HFHD,3次/周,4 h/次,对比不同透析模式对患者血压的影响。结果 实施HFHD后患者的平均动脉压(MAP)有所降低,在第3 h与第4 h透析后,血压把控优于LFHD(P<0.05)。结论 对于MHD老年患者来说,实施HFHD是优良的透析方法。     

全国著名骨伤专家梁铁民教授学术思想和正骨经验

总结了全国著名骨伤专家梁铁民教授的学术思想和正骨经验,简述了梁老生平。梁老学术思想表现在突出整体观念,主张辨证施术;注重调理气血,强调药物接续;重视望问切触量法五诊结合等三个方面。对于梁老正骨经验先进行了综合论述,进一步佐证其学术思想;后分别从小儿桡骨头半脱位、颈椎错位、胸腰椎小关节错位、肋骨骨折等梁老研究较深入和比较擅长的几个方面进行了阐述。特别是颈椎错位这种高难度高风险的手法操作,体现出梁老高超的手法技艺。     

Haemodynamic profiles of etomidate vs propofol for induction of anaesthesia: a randomised controlled trial in patients undergoing cardiac surgery

Background

Etomidate is frequently selected over propofol for induction of anaesthesia because of a putatively favourable haemodynamic profile, but data confirming this perception are limited.